Department of Anesthesiology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, P.R. China.
Department of Anesthesiology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, P.R. China.
Toxicol Mech Methods. 2022 Jul;32(6):453-462. doi: 10.1080/15376516.2022.2042881. Epub 2022 Mar 10.
This study aimed to investigate the role and mechanism of long non-coding RNA maternally expressed gene 3 (MEG3) in cognitive dysfunction induced by isoflurane (ISO). Morrier water maze analysis was performed to evaluate the cognitive function of rats. Modified modified neurological severity score (mNSS) scores were assessed for neurological damage. The levels of MEG3 in hippocampal tissues of rats and hippocampal neuron cell lines HT22 were examined by reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Moreover, the cell viability and apoptosis were assessed by the Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Indicators of inflammation and oxidative stress were determined using enzyme-linked immunosorbent assay (ELISA) and commercial assay kits. Relationship between MEG3 and microRNA (miR)-7-5p was verified by the dual-luciferase reporter gene assay. MEG3 was increased in hippocampal tissues and HT22 after ISO treatment ( < 0.05). MEG3 downregulation alleviated the increase in neurological severity score and cognitive dysfunction caused by ISO treatment ( < 0.05). In vitro, MEG3 downregulation alleviates the decrease in cell activity and increased apoptosis induced by ISO. What's more, MEG3 reduction eliminated activation of neuroinflammation and oxidative stress promoted by ISO treatment in rats and HT22 ( < 0.05). MEG3 was confirmed to specifically bind to miR-7-5p. Inhibition of miR-7-5p eliminated the alleviating effects of MEG3 downregulation on cognitive dysfunction caused by ISO treatment. Decreased MEG3 alleviates cognitive dysfunction caused by ISO by targeting miR-7-5p and play a neuroprotective effect. We present a strategy for MEG3 as a potential target for brain protection during anesthesia.
本研究旨在探讨长非编码 RNA 母系表达基因 3（MEG3）在异氟烷（ISO）诱导认知功能障碍中的作用和机制。通过 Morris 水迷宫分析评估大鼠的认知功能。改良的改良神经严重程度评分（mNSS）用于评估神经损伤。通过逆转录定量聚合酶链反应（qRT-PCR）检测大鼠海马组织和海马神经元细胞系 HT22 中 MEG3 的水平。此外，通过细胞计数试剂盒-8（CCK-8）和流式细胞术检测细胞活力和凋亡。通过酶联免疫吸附测定（ELISA）和商业检测试剂盒测定炎症和氧化应激指标。通过双荧光素酶报告基因检测验证 MEG3 与 microRNA（miR）-7-5p 之间的关系。ISO 处理后，大鼠海马组织和 HT22 中 MEG3 增加（<0.05）。MEG3 下调减轻 ISO 处理引起的神经严重程度评分和认知功能障碍增加（<0.05）。在体外，MEG3 下调减轻 ISO 引起的细胞活性降低和凋亡增加。此外，MEG3 减少消除了 ISO 处理诱导的大鼠和 HT22 中神经炎症和氧化应激的激活（<0.05）。MEG3 被证实可以特异性结合 miR-7-5p。抑制 miR-7-5p 消除了 MEG3 下调对 ISO 处理引起的认知功能障碍的缓解作用。减少 MEG3 通过靶向 miR-7-5p 减轻 ISO 引起的认知功能障碍，发挥神经保护作用。我们提出了一种以 MEG3 为靶点的麻醉期间脑保护策略。
